Effect Of Chronic Pretreatment With 17?-estradiol And/or Progesterone On The Nociceptive Response To Uterine Cervical Distension In A Rat Model

Background:A large number of experimental studies and clinical observations have found that females are more susceptible than males to numerous visceral and somatic pain syndromes,such as fibromyalgia,menopause-related back pain,migraine.This phenomenon is interpreted as a consequence of the gonadal hormone modulation of pain perception and transduction.The pain of childbirth is one of the most severe pain for the majority of women in their life.The distension of the cervix is the main source of pain during labor.The uterine cervical dilatation?UCD?model serves as a useful animal model for the study of acute visceral pain associated with acute cervical dilatation.Visceral motor response?VMR?has been widely evaluated as a reliable indicator of visceral nociception in animals.Immediate early gene c-fos expression was considered as an indicator of noxiously activated spinal neurons.Objection:In this study,we focused on the roles of 17?-estradiol and progesterone in visceralnociception with the use of a rat model of uterine cervical distension.Female ovariectomized rats were injected with 17?-estradiol?E₂?or progesterone?P₄?for 21days,after which visceral pain-induced spinal c-fos expression and visceromotor reflex changes were compared between ovariectomized and hormone-substituted groups.Materials and Methods:Part ?:Clean,non-pregnant,female Sprague-Dawley rats,weighing 200 to 250 g.10of the rats were randomized in 2 groups?n=5?:Sham group?Sham??group of uterine cervical distension?UCD?.Each distension lasted for 1 hour and then recoverd for 30minutes.Electromyogram?EMG?signals were monitored using the Medlab-U/4C biosignal system.After female hormone therapy,T12-S1 spinal cord segments were taken for immunohistochemical staining.Part ?:Clean,non-pregnant,female Sprague-Dawley rats,weighing 200 to 250 g.Rats were divided into six groups:the sham surgery?UCD?,ovariectomized?OVX?,OVX with oil?OVX+OIL?,OVX with 17?-estradiol replacement?OVX+E₂?,OVX with progesterone replacement?OVX+P₄?,and OVX with 17?-estradiol and progesterone replacement?OVX+E₂+P₄?groups.All of the rats were subjected to UCD at the end of a 21-day hormone or vehicle replacement?n=6 per group?.We recorded the c-fos expression and EMG signals induced by UCD.Results:We found that uterine cervical distension induced a drastic increase in spinal c-fos expression and visceromotor reflex activity,and ovariectomy inhibited the increase in c-fos expression induced by visceral pain;this inhibition was reversed by estrogen but not progesterone replacement.Conclusions:This study indicates that estrogen is involved in uterine cervical nociception,while progesterone plays less of a significant role.